Regulation of c-Myb activity by tumor suppressor p53

Heat shock proteins (HSPs) act as chaperones and play important roles durin g cellular proliferation and apoptosis. Heat shock factors (HSFs) mediate t ranscriptional induction of HSP genes. Among multiple heat shock transcript ion factors (HSFs) in vertebrates, HSF3 is specifically activated in unstre ssed proliferating cells by direct binding to the c-myb proto-oncogene prod uct (c-Myb), Since c-Myb has an important role in cellular proliferation, t his regulatory pathway suggests a link between the events of cellular proli feration and the stress response. The c-Myb-induced activation of HSF3 is n egatively regulated by the p53 tumor suppressor protein. p53 directly binds to HSF3 and blocks the interaction between c-Myb and HSF3, In addition, p5 3 stimulates the degradation of c-Myb, which is, at least partly, mediated by induction of Siah in certain types of cells. Thus, c-Myb and p53 regulat e the expression of HSPs via HSF3 in opposite: ways. (C) 2001 Academic Pres s.